The human tissue kallikrein (KLK) gene family contains 15 members that play important roles in cancer. Notably, kallikrein-1, also known as tissue kallikrein, cleaves kininogen to release the vasoactive kinin peptide, bradykinin or lysyl-bradykinin. Kallikrein-3, called prostate specific antigen (PSA), is an established tumor marker that aids in the diagnosis, staging, and follow up of prostate cancer. Kallikrein-4 is specifically expressed in the prostate and over-expressed in prostate cancer. Kallikrein-5 is widely expressed but found at high levels in skin, breast, brain and testis; over-expression is an indicator of poor prognosis in ovarian cancer. Kallikrein-8 is expressed in the brain and is a novel marker of ovarian and cervical cancer.

Human plasma kallikrein, a serine protease, is synthesized in the liver and circulates in the plasma bound to high molecular weight (HMW) kininogen or as a free zymogen. Once activated by its physiological activator, coagulation factor XII, it displays endopeptidase activity towards peptide bonds after arginine (preferred) and lysine. It cleaves HMW kininogen, its major physiological substrate, to release the potent vasodilator peptide bradykinin. It is also able to cleave a number of inactive precursor proteins to generate active products, such as plasminogen and prourokinase.